Lab AnimalPub Date : 2024-09-17DOI: 10.1038/s41684-024-01439-7
Kaylynn Monarch, Junchul Yoon, Kyungjun Uh, Emily Reese, Diana Canaveral Restrepo, Darling Melany de Carvalho Madrid, Laurie Touchard, Lee D. Spate, Melissa S. Samuel, John P. Driver, Ji-Hey Lim, Sarah Schlink, Kristin M. Whitworth, Kevin D. Wells, Randall S. Prather, Paula R. Chen, Kiho Lee
{"title":"Fetal bone engraftment reconstitutes the immune system in pigs with severe combined immunodeficiency","authors":"Kaylynn Monarch, Junchul Yoon, Kyungjun Uh, Emily Reese, Diana Canaveral Restrepo, Darling Melany de Carvalho Madrid, Laurie Touchard, Lee D. Spate, Melissa S. Samuel, John P. Driver, Ji-Hey Lim, Sarah Schlink, Kristin M. Whitworth, Kevin D. Wells, Randall S. Prather, Paula R. Chen, Kiho Lee","doi":"10.1038/s41684-024-01439-7","DOIUrl":"10.1038/s41684-024-01439-7","url":null,"abstract":"Genetic modification of genes such as recombination activating gene 2 (RAG2) or interleukin-2 receptor-γ (IL2RG) results in pigs exhibiting severe combined immunodeficiency (SCID). Pigs presenting a SCID phenotype are important animal models that can be used to establish xenografts and to study immune system development and various immune-related pathologies. However, due to their immunocompromised nature, SCID pigs have shortened lifespans and are notoriously difficult to maintain. The failure-to-thrive phenotype makes the establishment of a breeding population of RAG2/IL2RG double-knockout pigs virtually impossible. Here, to overcome this limitation, we investigated whether reconstituting the immune system of SCID piglets with a fetal bone allograft would extend their lifespan. Following intramuscular transplantation, allografts gave rise to lymphocytes expressing T cell (CD3, CD4 and CD8), B cell (CD79α) and natural killer cell (CD335) lineage markers, which were detected in circulation as well in the spleen, liver, bone marrow and thymic tissues. The presence of lymphocytes indicates broad engraftment of donor cells in the recipient SCID pigs. Unlike unreconstituted SCID pigs, the engrafted animals thrived and reached puberty under standard housing conditions. This study demonstrates a novel method to extend the survival of SCID pigs, which may improve the availability and use of SCID pigs as a biomedical animal model. Severe combined immunodeficiency (SCID) pigs do not live long enough to reproduce naturally. Monarch et al. show that reconstituting the immune system of SCID piglets with fetal bone allografts extends their lifespan, allowing them to reach puberty.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01439-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab AnimalPub Date : 2024-08-30DOI: 10.1038/s41684-024-01437-9
Alexandra Le Bras
{"title":"Role of oligodendrocytes in Aβ plaque burden","authors":"Alexandra Le Bras","doi":"10.1038/s41684-024-01437-9","DOIUrl":"10.1038/s41684-024-01437-9","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01437-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab AnimalPub Date : 2024-08-30DOI: 10.1038/s41684-024-01435-x
Jorge Ferreira
{"title":"Glutathione is essential for liver lipid metabolism","authors":"Jorge Ferreira","doi":"10.1038/s41684-024-01435-x","DOIUrl":"10.1038/s41684-024-01435-x","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab AnimalPub Date : 2024-08-30DOI: 10.1038/s41684-024-01428-w
Alexandra Le Bras
{"title":"A new zebrafish model of SHH medulloblastoma","authors":"Alexandra Le Bras","doi":"10.1038/s41684-024-01428-w","DOIUrl":"10.1038/s41684-024-01428-w","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab AnimalPub Date : 2024-08-30DOI: 10.1038/s41684-024-01438-8
Jorge Ferreira
{"title":"Kaempferol-3-rhamnoside can help treat diabetes in mice","authors":"Jorge Ferreira","doi":"10.1038/s41684-024-01438-8","DOIUrl":"10.1038/s41684-024-01438-8","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01438-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab AnimalPub Date : 2024-08-30DOI: 10.1038/s41684-024-01436-w
Alexandra Le Bras
{"title":"Effect of housing temperature on drug-induced weight loss","authors":"Alexandra Le Bras","doi":"10.1038/s41684-024-01436-w","DOIUrl":"10.1038/s41684-024-01436-w","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01436-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lab AnimalPub Date : 2024-08-30DOI: 10.1038/s41684-024-01431-1
Alexandra Le Bras
{"title":"Metformin treatment for fragile X syndrome","authors":"Alexandra Le Bras","doi":"10.1038/s41684-024-01431-1","DOIUrl":"10.1038/s41684-024-01431-1","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142101881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Production of a heterozygous exon skipping model of common marmosets using gene-editing technology","authors":"Kenya Sato, Hiroki Sasaguri, Wakako Kumita, Tetsushi Sakuma, Tomoe Morioka, Kenichi Nagata, Takashi Inoue, Yoko Kurotaki, Naomi Mihira, Michihira Tagami, Ri-ichiroh Manabe, Kokoro Ozaki, Yasushi Okazaki, Takashi Yamamoto, Makoto Suematsu, Takaomi C. Saido, Erika Sasaki","doi":"10.1038/s41684-024-01424-0","DOIUrl":"10.1038/s41684-024-01424-0","url":null,"abstract":"Nonhuman primates (NHPs), which are closely related to humans, are useful in biomedical research, and an increasing number of NHP disease models have been reported using gene editing. However, many disease-related genes cause perinatal death when manipulated homozygously by gene editing. In addition, NHP resources, which are limited, should be efficiently used. Here, to address these issues, we developed a method of introducing heterozygous genetic modifications into common marmosets by combining Platinum transcription activator-like effector nuclease (TALEN) and a gene-editing strategy in oocytes. We succeeded in introducing the heterozygous exon 9 deletion mutation in the presenilin 1 gene, which causes familial Alzheimer’s disease in humans, using this technology. As a result, we obtained animals with the expected genotypes and confirmed several Alzheimer’s disease-related biochemical changes. This study suggests that highly efficient heterozygosity-oriented gene editing is possible using TALEN and oocytes and is an effective method for producing genetically modified animals. This study shows that using gene-editing technology in oocytes using Platinum TALEN is an effective method for producing genetically modified marmosets by exon skipping.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01424-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}